Aggression is one of most enduring, complex, and problematic forms of human social interaction. The consequences of human aggression extract a substantial toll on public health and criminal justice systems, communities, families, and individuals. The relationship between alcohol abuse and aggression has been well documented. Studying this relationship through the integration of methodologies in brain imaging, psychopharmacology, and laboratory behavioral science will further scientific understanding of this complex phenomenon, and may provide inroads for treatment strategies aimed at decreasing the probability of alcohol-related violence. Accordingly, the primary objectives of this application are to utilize functional magnetic resonance imaging (fMRI) to (a) examine neural correlates that mediate the relationship between human aggressive behavior and chronic alcohol abuse, and (b) examine the examine neural correlates of changes in human aggressive behavior produced by acute alcohol administration. Specifically, two experiments will be conducted. The first experiment will use a laboratory model of human aggressive behavior (the Point Subtraction Aggression Paradigm, or PSAP) adapted for use during fMRI, to study differences in brain networks underlying aggressive behavior among alcohol dependent and matched healthy control participants. The second experiment will examine the effects of acute alcohol administration on aggressive behavior in non-alcohol dependent social drinkers, using the PSAP for fMRI to determine critical brain regions and networks involved in alcohol-induced human aggression. The PSAP methodology has well established reliability and validity, and utilizes a multiple response option procedure offering monetary earning and aggressive response options (cued by provocations in the form of monetary subtractions attributed to another individual). Across dozens of studies, the PSAP has been demonstrated to be sensitive to both acute drug effects (including alcohol) and differences in clinical groups (including substance abusers). The procedure has been adapted for use during fMRI, accounting for critical visual and temporal variables, and is able to identify brain regions that are uniquely active during aggressive behavior. Consequently, fMRI scans will be acquired during PSAP sessions to measure regional brain activation. In experiment 1, steady-state data will be acquired in pre-scanning PSAP sessions acquired using a mock scanner. Once levels of aggressive behavior are stable, repeated PSAP sessions will be conducted during fMRI scanning individuals meeting criteria for alcohol dependence and healthy matched controls. In experiment 2, alcohol and placebo will be acutely administered to non-dependent social drinkers during repeated PSAP sessions conducted under fMRI, using a within-subject counterbalanced design. PUBLIC HEALTH RELEVANCE: This project seeks to further scientific understanding of the neurobiological factors that mediate the relationship between alcohol use and human aggression. Specifically, a well-established laboratory paradigm of human aggression (PSAP) has been adapted for use under functional MRI. This procedure will be used to study the neural correlates of aggression in alcohol-dependent vs. matched healthy control groups (Experiment 1), and to study the acute effects of alcohol on aggression (Experiment 2).